DESCRIPTION: This project will synthesize conformal adhesive compliant hydrogel-based microelectrode arrays for stimulating small diameter peripheral nerves. Peripheral nerve interfaces (PNI) are neuromodulation devices that measure and/or stimulate the peripheral nervous system (PNS). Current multielectrode array designs for PNI include penetrating devices, cuff electrodes, and regenerative electrodes. Next-generation neuromodulation technologies that measure and stimulate the PNS are facing a materials-related bottleneck. Penetrating multielectrode arrays for PNI are promising, but suboptimal because glial responses isolate the sensor from neurons over time. Cuff electrodes and regenerative electrode geometries are also suboptimal. A non- destructive device that can stably integrate with the PNS without damaging tissue could accelerate the translation of peripheral nerve stimulation therapies. Here we propose an electrode material that will exhibit a combination of chemical, electrical, and mechanical properties to promote non-destructive wound-free facile integration with the PNS. The key innovation will be bioinspired adhesive hydrogel substrates that will permit transfer printing of high-density electrode arrays to ultracompliant hydrated substrates. Adhesion-promoting hydrogels will also enhance conformal lamination at the tissue-device interface. The performance of hydrogel- based electrode arrays will be assessed using feline models. In vivo stimulation thresholds will be measured in the sciatic nerve of anesthetized felines. Hydrogel-based MEA will be fabricated and integrated with stimulation/recording hardware. Fascicular selectivity during stimulation will be assessed by mapping hindlimb muscle recruitment across many muscles as a function of electrode stimulation sequences. Furthermore, recruitment curves will be quantified as a function of stimulation intensity. This project will generate and validate a new class of bioinspired hydrogel-based devices that are ideally suited for improving tissue-device integration between PNI and the PNS. The prospective primary knowledge and materials design strategies described here are generalizable to other medical device technologies. Next-generation materials and fabrication strategies could improve the performance many types of implantable bioelectronics devices such as electrocorticography (ECoG) BMI, pacemaker leads, retinal prosthetics, and electronically active scaffolds for tissue regeneration.